INSTITUTE
OF GENETICS & CYTOLOGY

Gilbert’s syndrome is the most common hereditary disorder of bilirubin metabolism (noted in 5-10% of Europeans). The genetic basis for the development of Gilbert’s syndrome in people of European descent is the presence of the mutation (TA)7 in a homozygous state (UGT1A1*28). The disease refers to pigment hepatoses and can lead to liver failure, and thereby, cause cholelithiasis. Glucuronosyltransferase, the product of the UGT1A1 gene, also catalyzes xenobiotic metabolism. The enzyme metabolizes a group of therapeutic drugs, which include gemfibrozil, atazanavir, irinotecan metabolites, simvastatin, atorvastatin, cerivastatin, buprenorphine etc.

Hemochromatosis is a hereditary liver disease that causes excessive iron accumulation in the body’s organs and tissues and leads to their failure as a result. Liver failure is a common and early sign of hereditary hemochromatosis. Patients with this disease carry, in 90% of cases, homozygous mutations in the fourth exon of the HFE gene causing the substitution of the 282nd amino acid cysteine ​​with tyrosine in the protein: C282Y. On average, every fifth European has another mutation in the second exon of the same gene where histidine in position 63 is replaced with asparagine: H63D. The phenotypic effect of this variant is significantly weaker compared to C282Y. The detection of HFE gene mutations allows the DNA diagnostics of patients suffering from hereditary hemochromatosis. Moreover, testing for HFE gene mutations is recommended to patients belonging to risk groups. First of all, these are pregnant women with gestational diabetes and/or chronic venous insufficiency.

Wilson’s disease is an autosomal recessive disorder associated with impaired copper excretion from the body, and its incidence in different populations is from 1:30 000 to 1:100 000. The disease is caused by mutations in the ATP7B gene encoding a copper-transporting enzyme. The H1069Q mutation in the ATP7B gene is most common in Europeans. Molecular genetic analysis for the presence of H1069Q mutation is an important step in confirming a hypothesis about the presence of Wilson’s disease in a patient. The genetic testing of this mutation will provide information on the carriage of the main pathogenic mutation of this gene as quickly as possible for the groups of individuals with a suspected diagnosis of Wilson’s disease or individuals burdened with other diseases where the presence of this pathogenic gene mutation may aggravate the course of the disease.

Alpha-1antitrypsin deficiency is a genetically determined disease that can manifest itself in the form of liver failure due to the accumulation of pathological alpha-1 antitrypsin in it. The alpha-1antitrypsin protein (A1AT) is encoded by the SERPINA1 gene or the Pi gene as it has been more frequently called in recent years. Liver diseases with A1AT deficiency occur in the case of mutations that lead to A1AT accumulation in liver cells. The classic type of such a mutation is the Pi*ZZ (G342K) genotype where polymerized A1AT molecules linger in the endoplasmic reticulum of liver cells and produce a hepatotoxic effect. In approximately 37% of patients with severe A1AT deficiency, in the case of the ZZ genotype liver cirrhosis develops. Another private allelic variant, S (G264V), acquires clinical significance when combined with Z variants. Genetic testing of mutant Pi alleles is one of the steps in the identification of causes of prolonged jaundice and other liver dysfunctions (mainly in children and adolescents).